The ultimate goal of the study is to map the progesterone specific binding site of the human uterine progesterone receptor. This will be achieved by affinity labeling techniques. Progesterone derivatives containing tritiated alkylating functions substituted at the 2 Alpha, 6 Beta, 11 Beta, 17 Alpha and 21 positions will be used. These derivatives have the capability of forming covalent bonds between the steroid and receptor. Hydrolysis of the resulting adducts followed by separation of the products will allow identification of the particular amino acids which have been alkylated by the radioactive progesterone analogues. We have already shown that by using the above method, a histidine and histidine and methionine residues were found to be located adjacent to the 11 Alpha- and 16 Alpha-positions respectively. Knowing the various amino-acid residues associated with particular atoms in the progesterone molecule, we should be able to predict which new compounds should be synthesized to fit the progesterone binding site with an affinity equal to or greater than that of progesterone. This information will be invaluable in our long-term quest to design hormonally inert agents which fit the receptor site to block progesterone binding. The reason for selecting human receptor for these studies is so that we can synthesize such an antiprogestin which will antagonize progesterone action in its target cells in the human. These agents may then prove useful as antifertility agents since the hormone progesterone is essential for all the physiological events associated with pregnancy.